CN103405443A - Chinese herbal medicine compound taxus chinensis lipidosome preparation for treating breast cancers and preparation method thereof - Google Patents
Chinese herbal medicine compound taxus chinensis lipidosome preparation for treating breast cancers and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a Chinese herbal medicine compound taxus chinensis lipidosome preparation for treating breast cancer and TNBC (Triple Negative Breast Cancer) and a preparation method thereof. The Chinese herbal medicine compound taxus chinensis lipidosome preparation is prepared from taxol and triptolide in weight proportion. According to the preparation method, lipidosome is prepared by adopting an ethanol injection method and the Chinese herbal medicine compound taxus chinensis lipidosome preparation is obtained further. Animal in-vivo anticancer pharmacological experiments prove that the Chinese herbal medicine compound taxus chinensis lipidosome preparation has an obvious inhibition effect on the growth of breast cancers and TNBC, and the anticancer activity of the Chinese herbal medicine compound taxus chinensis lipidosome preparation is obviously higher than that of a chemotherapeutic drug 5- fluorouracil. The anticancer effect of the Chinese herbal medicine compound taxus chinensis lipidosome preparation is better than that of a Chinese herbal medicine compound taxus chinensis non-lipidosome preparation.
Description
One, technical field
The present invention relates to the Chinese medicine technical field, specifically relate to a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma (breast carcinoma and three negative breast cancer) and preparation method thereof.
Two, background technology
Cancer is the formidable enemy of harm humans health.The annual new cases of cancer of China approximately has 1,600,000 people, and that dies from cancer every year approximately has 1,300,000 people, rises year by year because of the dead number of cancer in the whole nation, and China is the zone occurred frequently of the cancers such as breast carcinoma, breast carcinoma, and cancer mortality is high.
There is no at present the most of cancer patients of effective cured substance.Though chemotherapeutics has certain curative effect to cancer, toxic and side effects is large, and Chinese patent medicine is generally lower to the curative effect of cancer, and curative effect is all undesirable.
The inventor is through the arduous anticancer active substance of studying the Chinese medicines such as Herba Phyllanthi Urinariae, Ramulus et folium taxi cuspidatae, dry maxima skin, Radix Tripterygii Wilfordii decades, therefrom extract multiple anti-cancer active compound, through anticancer experimentation, show, the cancerous cell such as human breast carcinoma, pulmonary carcinoma, hepatocarcinoma and zoografting carcinoma are all had to significant inside and outside anticancer therapy effect, and applied for obtaining 10 antineoplastic product invention patent certificates and (as the patent No., be respectively: ZL200810124590.3; ZL200810124588.6; ZL201210033666.8 etc.).On the basis of above-mentioned research, the inventor studies again and has invented a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma and preparation method thereof, and its active anticancer is high, toxicity is low.
Three, summary of the invention
1, goal of the invention: the purpose of this invention is to provide the anti-breast cancer medicines that a kind of active anticancer is high, toxicity is low, specifically take a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma prepared as raw material by paclitaxel, triptolide and preparation method thereof.
2, technical scheme:
A kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma (breast carcinoma and three negative breast cancer) of the present invention, it is characterized in that it is by the compound taxol composition Liposomal formulation that paclitaxel, triptolide form, each Chinese medicine ingredients brief introduction is as follows:
Paclitaxel (Paclitaxe, Taxol, TAX), (claiming again: taxol, Paclitaxe, Paclitaxe), molecular formula: C
47H
51NO
14, molecular weight: 853.89, chemical structural formula:
Triptolide (triptolide, TL), (claim again: Radix Tripterygii Wilfordii lactone alcohol), molecular formula: C
20H
24O
6, molecular weight: 360.4.
Chemical structural formula:
A kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma, it is characterized in that said preparation is made by Chinese medicine compound and the liposome of following percentage by weight: Chinese medicine compound Ramulus et folium taxi cuspidatae composition: liposome is 1:30, and wherein Chinese medicine compound Ramulus et folium taxi cuspidatae composition is 1~2 part of paclitaxel, 1~2 part of triptolide; Wherein liposome component is by lecithin: amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine: cholesterol is 10:1:1.
Described a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma, is characterized in that described breast carcinoma also comprises three negative breast cancer.
The Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation of described treatment breast carcinoma is characterized in that the preparation process of said preparation is as follows:
(1) proportioning raw materials for preparing liposome is: the weight ratio of lecithin and amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine is 10:1, and the weight ratio of lecithin and cholesterol is 10:1;
(2) weight ratio of liposome and Chinese medicine compound Ramulus et folium taxi cuspidatae composition is 30:1;
(3) preparation method of Chinese medicine compound Ramulus et folium taxi cuspidatae liposome adopts the alcohol injection preparation: get the PBS buffer of pH7.4 in eggplant type bottle, in 50~55 ℃ of preheating 30~35min of water bath with thermostatic control;
(4) get the liposome raw material of heavy amount proportioning of step 1 and 2 and Chinese medicine compound Ramulus et folium taxi cuspidatae composition in beaker, add appropriate dehydrated alcohol to make its dissolving;
(5) after all dissolving, Chinese medicine compound Ramulus et folium taxi cuspidatae composition is injected into rapidly in the eggplant type bottle that buffer solution is housed of step 3 constant temperature preheating, obtain the milky liposome turbid liquor, continue to stir aquation 1~1.2h, evacuation is except ethanol, 800P crosses 10~12 circulations of high pressure dispersing emulsification machine, obtains Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation.
The application of described compound taxol composition Liposomal formulation in preparation treatment breast cancer medicines.
The application of described compound taxol composition Liposomal formulation in preparation treatment three negative breast cancer medicines.
Described compound taxol composition Liposomal formulation has obvious inhibitory action to the growth of breast carcinoma and three negative breast cancer in vivo, and its active anticancer is apparently higher than the chemotherapeutic 5-fluorouracil.
The described compound taxol composition Liposomal formulation inhibitory action to growth of breast cancers in vivo is higher than the non-Liposomal formulation of compound taxol composition.
3, beneficial effect:
A kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma of the present invention, to take anticarcinogen prepared as raw material by paclitaxel, triptolide, through Anticancer experiment in animal body, the growth of breast carcinoma (breast carcinoma and three negative breast cancer) is had to the inhibitory action of highly significant.The Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation of 9mg/kg dosage can significantly suppress the growth (P<0.01) of nude mice transplanted breast carcinoma and three negative breast cancer, and its tumour inhibiting rate is respectively 68.57%, 64.55%; Its active anticancer to breast carcinoma and three negative breast cancer is higher than chemotherapeutic 5-fluorouracil (P<0.01), also higher than the single composition (paclitaxel single, triptolide single) of prescription.The Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation inhibitory action to growth of breast cancers in vivo is higher than the non-Liposomal formulation of Chinese medicine compound Ramulus et folium taxi cuspidatae composition.Can be used for treating breast carcinoma and three negative breast cancer.This provides very promising efficient preliminary election medicine for improving anticancer clinical efficacy, and also the mechanism for the Study of Traditional Chinese Medicine components compatibility provides good component prescription.
Four, the specific embodiment
Embodiment 1: a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma and preparation method thereof, and the preparation method step is as follows:
(1) weight of Chinese medicine compound Ramulus et folium taxi cuspidatae composition is: paclitaxel 18mg, triptolide 18mg.
(2) liposome raw materials proportioning is lecithin 900mg, amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine 90mg, cholesterol 90mg;
(3) method for preparing lipidosome adopts the alcohol injection preparation, and precision measures the PBS buffer 90mL of pH7.4 in eggplant type bottle, in 50 ℃ of preheating 35min of water bath with thermostatic control;
(4) the liposome raw material of getting step 2 proportioning, in beaker, adds the Chinese medicine compound Ramulus et folium taxi cuspidatae composition 36mg of step 1, then adds appropriate dehydrated alcohol to make its dissolving;
(5) after all dissolving, Chinese medicine compound Ramulus et folium taxi cuspidatae composition is injected into rapidly in the eggplant type bottle that buffer solution is housed of step 3 constant temperature preheating, obtain the milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, 800P crosses 10 circulations of high pressure dispersing emulsification machine, obtains Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation.
Embodiment 2: a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma and preparation method thereof, and the preparation method step is as follows:
(1) weight of Chinese medicine compound Ramulus et folium taxi cuspidatae composition is: paclitaxel 8mg, triptolide 16mg.
(2) liposome raw materials proportioning is lecithin 600mg, amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine 60mg, cholesterol 60mg;
(3) method for preparing lipidosome adopts the alcohol injection preparation, and precision measures the PBS buffer 90mL of pH7.4 in eggplant type bottle, in 55 ℃ of preheating 30min of water bath with thermostatic control;
(4) the liposome raw material of getting step 2 proportioning, in beaker, adds the Chinese medicine compound Ramulus et folium taxi cuspidatae composition 24mg of step 1, then adds appropriate dehydrated alcohol to make its dissolving;
(5) after all dissolving, Chinese medicine compound Ramulus et folium taxi cuspidatae composition is injected into rapidly in the eggplant type bottle that buffer solution is housed of step 3 constant temperature preheating, obtain the milky liposome turbid liquor, continue to stir aquation 1.2h, evacuation is except ethanol, 800P crosses 12 circulations of high pressure dispersing emulsification machine, obtains Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation.
Embodiment 3: a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma and preparation method thereof, and the preparation method step is as follows:
(1) weight of Chinese medicine compound Ramulus et folium taxi cuspidatae composition is: paclitaxel 24mg, triptolide 12mg.
(2) liposome raw materials proportioning is lecithin 900mg, amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine 90mg, cholesterol 90mg;
(3) method for preparing lipidosome adopts the alcohol injection preparation, and precision measures the PBS buffer 90mL of pH7.4 in eggplant type bottle, in 50 ℃ of preheating 35min of water bath with thermostatic control;
(4) the liposome raw material of getting step 2 proportioning, in beaker, adds the Chinese medicine compound Ramulus et folium taxi cuspidatae composition 36mg of step 1, then adds appropriate dehydrated alcohol to make its dissolving;
(5) after all dissolving, Chinese medicine compound Ramulus et folium taxi cuspidatae composition is injected into rapidly in the eggplant type bottle that buffer solution is housed of step 3 constant temperature preheating, obtain the milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, 800P crosses 10 circulations of high pressure dispersing emulsification machine, obtains Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation.
Embodiment 4: the inhibitory action of a kind of compound taxol composition Liposomal formulation to the nude mice transplanted breast carcinoma
1, laboratory animal and tumor strain
The BALB/C-nu nude mice, 70, female, in 4~6 ages in week, body weight 18-20g, purchased from zoopery center, this school.Human breast cancer cell strain MCF-7, purchased from zoopery center, institute of oncology, Jiangsu Province.
2, modeling and experimental technique
70 of BALB/C-nu nude mices, stay 10 negative matched groups in proportion at random, and all the other 60 are carried out modeling.Get the exponential phase MCF-7 Human Breast Cancer Cells of In vitro culture, cell concentration is adjusted into 1 * 10
7/ ml.Under aseptic condition, MCF-7 Human Breast Cancer Cells is inoculated in to BALB/C-nu nude mice back, inoculum concentration is that only (cell number is 2 * 10 to 0.2ml/
6/ only).Whole seeded process must be carried out with sterile working in aseptic cover, in 1h, complete inoculation.
After inoculation, be divided at random 6 groups, 10 every group, be respectively the tumor model matched group, compound taxol composition liposome, the non-liposome of compound taxol composition and 4 test group of composition single thereof, 5-fluorouracil (5-FU) positive controls, separately add negative control group, totally 7 groups.
After inoculation oncocyte 24h, test group lumbar injection compound taxol composition liposome, the non-liposome of compound taxol composition, paclitaxel single, triptolide single, dosage is 9mg/kg, negative control group and tumor model matched group lumbar injection equal-volume injectable drug solvent, the 5-FU matched group be take normal saline and is solvent, dosage is 9mg/kg, each treated animal all by 0.2ml at lumbar injection, 3 weeks of successive administration.Next day after the last administration, carry out following observation:
Completely peel off the tumor piece, and the calculating tumor control rate of weighing, tumor control rate=(model control group tumor weight-test of cure group tumor weight)/model control group tumor weight * 100%.
3, experimental result:
The inhibitory action of a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation to the nude mice transplanted breast carcinoma: 9mg/kg Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation can significantly suppress the growth (P<0.01) of nude mice transplanted breast carcinoma, its anti-breast cancer activity is higher than non-liposome compound taxol composition (P<0.01), non-lipidosome Chinese traditional medicine compound taxol composition anti-breast cancer activity is again higher than chemotherapeutic 5-fluorouracil (P<0.01), also higher than the single composition (paclitaxel single, triptolide single) of prescription.In Table 1.
The inhibitory action of table 1 Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation to the growth of nude mice transplanted breast carcinoma
Embodiment 5: the inhibitory action of a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation to nude mice transplantability three negative breast cancer
1, laboratory animal and tumor strain
The BALB/C-nu nude mice, 70, female, in 4~6 ages in week, body weight 18-20g, purchased from zoopery center, this school.People three negative breast cancer cell strain MDA-MB-231, purchased from zoopery center, institute of oncology, Jiangsu Province.
2, modeling and experimental technique
70 of BALB/C-nu nude mices, stay 10 negative matched groups in proportion at random, and all the other 60 are carried out modeling.Get the exponential phase human breast carcinoma MDA-MB-231 cell of In vitro culture, cell concentration is adjusted into 1 * 10
7/ ml.Under aseptic condition, human breast carcinoma MDA-MB-231 cell is inoculated in to BALB/C-nu nude mice back, inoculum concentration is that only (cell number is 2 * 10 to 0.2ml/
6/ only).Whole seeded process must be carried out with sterile working in aseptic cover, in 1h, complete inoculation.
After inoculation, be divided at random 6 groups, 10 every group, be respectively the tumor model matched group, compound taxol composition liposome, the non-liposome of compound taxol composition and 4 test group of composition single thereof, 5-fluorouracil (5-FU) positive controls, separately add negative control group, totally 7 groups.
After inoculation oncocyte 24h, test group lumbar injection compound taxol composition liposome, the non-liposome of compound taxol composition, paclitaxel single, triptolide single, dosage is 9mg/kg, negative control group and tumor model matched group lumbar injection equal-volume injectable drug solvent, the 5-FU matched group be take normal saline and is solvent, dosage is 9mg/kg, each treated animal all by 0.2ml at lumbar injection, 3 weeks of successive administration.Next day after the last administration, carry out following observation:
Completely peel off the tumor piece, and the calculating tumor control rate of weighing, tumor control rate=(model control group tumor weight-test of cure group tumor weight)/model control group tumor weight * 100%.
3, experimental result:
The inhibitory action of a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation to nude mice transplantability three negative breast cancer: 9mg/kg Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation can significantly suppress the growth (P<0.01) of nude mice transplantability three negative breast cancer, its anti-three negative breast cancer activity are higher than non-liposome compound taxol composition (P<0.01), the anti-three negative breast cancer activity of non-lipidosome Chinese traditional medicine compound taxol composition are again higher than chemotherapeutic 5-fluorouracil (P<0.01), also higher than the single composition (paclitaxel single, triptolide single) of prescription.In Table 2.
The inhibitory action of table 2 Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation to the three negative breast cancer growths of nude mice transplantability
Claims (7)
1. Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma, it is characterized in that said preparation is made by Chinese medicine compound Ramulus et folium taxi cuspidatae composition and the liposome of following percentage by weight: Chinese medicine compound Ramulus et folium taxi cuspidatae composition: liposome is 1:30, and wherein Chinese medicine compound Ramulus et folium taxi cuspidatae composition is 1~2 part of paclitaxel, 1~2 part of triptolide; Wherein liposome component is by lecithin: amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine: cholesterol is 10:1:1.
2. a kind of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma according to claim 1, is characterized in that described breast carcinoma also comprises three negative breast cancer.
3. the Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation for the treatment of breast carcinoma according to claim 1 is characterized in that the preparation process of said preparation is as follows:
(1) proportioning raw materials for preparing liposome is: the weight ratio of lecithin and amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine is 10:1, and the weight ratio of lecithin and cholesterol is 10:1;
(2) weight ratio of liposome and Chinese medicine compound Ramulus et folium taxi cuspidatae composition is 30:1;
(3) preparation method of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation adopts the alcohol injection preparation: get the PBS buffer of pH7.4 in eggplant type bottle, in 50~55 ℃ of preheating 30~35 min of water bath with thermostatic control;
(4) get the liposome raw material of heavy amount proportioning of step 1 and 2 and Chinese medicine compound Ramulus et folium taxi cuspidatae composition in beaker, add appropriate dehydrated alcohol to make its dissolving;
(5) after all dissolving, Chinese medicine compound Ramulus et folium taxi cuspidatae composition is injected into rapidly in the eggplant type bottle that buffer solution is housed of step 3 constant temperature preheating, obtain the milky liposome turbid liquor, continue to stir aquation 1~1.2 h, evacuation is except ethanol, 800 P cross 10~12 circulations of high pressure dispersing emulsification machine, obtain Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation.
4. the application of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation as claimed in claim 1 in preparation treatment breast cancer medicines.
5. the application of Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation as claimed in claim 1 in preparation treatment three negative breast cancer medicines.
6. Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation as claimed in claim 1 or 2 has obvious inhibitory action to the growth of breast carcinoma and three negative breast cancer in vivo, and its active anticancer is apparently higher than the chemotherapeutic 5-fluorouracil.
7. inhibitory action to growth of breast cancers is higher than the non-Liposomal formulation of compound taxol composition in vivo for Chinese medicine compound Ramulus et folium taxi cuspidatae composition Liposomal formulation as claimed in claim 1.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105233292A (en) * | 2015-10-19 | 2016-01-13 | 中国科学院北京基因组研究所 | Application of ORY-1001 to treatment of triple negative breast cancer through combined radiotherapy and chemotherapy |
CN105434446A (en) * | 2015-11-21 | 2016-03-30 | 中南大学湘雅医院 | Triptolide containing herbal medicine compound plaster as well as preparation method and application thereof |
CN105853682A (en) * | 2016-05-11 | 2016-08-17 | 张士舜 | Traditional Chinese medicinal composition for treating breast cancer and preparation method of traditional Chinese medicinal composition |
CN113855721A (en) * | 2021-08-04 | 2021-12-31 | 重庆赛诺生物药业股份有限公司 | Compound taxus chinensis capsule, preparation method and application of compound taxus chinensis capsule in qi deficiency and phlegm stasis syndrome in breast cancer chemotherapy |
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2013
- 2013-08-19 CN CN2013103606199A patent/CN103405443A/en active Pending
Non-Patent Citations (1)
Title |
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朱四红等: "雷公藤内酯醇联合紫杉醇对人卵巢癌耐顺铂细胞株体外活性的影响及机制", 《山东医药》 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105233292A (en) * | 2015-10-19 | 2016-01-13 | 中国科学院北京基因组研究所 | Application of ORY-1001 to treatment of triple negative breast cancer through combined radiotherapy and chemotherapy |
CN105233292B (en) * | 2015-10-19 | 2018-03-13 | 中国科学院北京基因组研究所 | The combined radiotherapies of ORY 1001 and chemotherapy are used for the purposes for treating people's triple negative breast cancer |
CN105434446A (en) * | 2015-11-21 | 2016-03-30 | 中南大学湘雅医院 | Triptolide containing herbal medicine compound plaster as well as preparation method and application thereof |
CN105434446B (en) * | 2015-11-21 | 2018-03-02 | 中南大学湘雅医院 | A kind of triptolide Chinese medicine compound prescription plastics and preparation method thereof, application |
CN105853682A (en) * | 2016-05-11 | 2016-08-17 | 张士舜 | Traditional Chinese medicinal composition for treating breast cancer and preparation method of traditional Chinese medicinal composition |
CN113855721A (en) * | 2021-08-04 | 2021-12-31 | 重庆赛诺生物药业股份有限公司 | Compound taxus chinensis capsule, preparation method and application of compound taxus chinensis capsule in qi deficiency and phlegm stasis syndrome in breast cancer chemotherapy |
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Application publication date: 20131127 |